Flow reduction stent grafts

Abstract

To provide an apparatus, a system and a method for altering blood flow in a vessel of a patient.SOLUTION: An apparatus, a system and a method may include restricting blood flow within a first side branch vessel to reduce flow into the first side branch and increase flow into one or more arteries distal to the first side branch vessel.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of Provisional Application No. 62 / 702,717, filed July 24, 2018, which is incorporated by reference in its entirety for all purposes.

[0002] The present disclosure relates to systems, medical devices and methods for treating heart failure and / or other cardiovascular diseases, and more particularly, to removing excess fluid accumulation typically resulting from underperfused kidneys. [Background technology]

[0003] Patients experiencing heart failure may have excess fluid accumulation in the body. Excess fluid accumulation can increase fluid accumulation in the interstitial spaces and worsen the patient's symptoms and quality of life. Excess fluid (or hypervolemia) is the leading cause of hospitalization in heart failure patients (approximately 1,000,000 cases per year in the United States).

[0004] Treatment of excess fluid accumulation can be treated pharmacologically with diuretics (or other pharmaceutical agents). However, patients may experience other problems such as drug resistance, undesirable side effects, inappropriate dosing, or non-compliance with drug instructions. Non-pharmaceutical options, such as implantable device solutions that provide alternatives or enhance drug efficacy by affecting renal function, can be beneficial to avoid these and other problems in treating excess fluid accumulation in the body. Similarly, chronic high blood pressure (hypertension) can also be managed pharmacologically with diuretics (or other antihypertensive drugs). In addition, other medical conditions can result in low blood pressure, reduced cardiac output, and reduced renal function. Insofar as the kidneys play a central role in regulating systemic blood pressure and fluid homeostasis, non-pharmaceutical options, such as implantable device solutions that provide alternatives or enhance drug efficacy by affecting renal function, can provide an alternative to manage fluid imbalances resulting from chronic medical conditions such as heart failure, hypertension, and other medical conditions. Summary of the Invention

[0005] In one example ("Example 1"), a method of altering blood flow within a blood vessel of a patient includes delivering an implantable medical device into the blood vessel, the implantable medical device including a stent element and a graft component attached to at least a portion of the stent element within the stent element, and positioning the implantable medical device to restrict blood flow in a first side branch vessel to reduce flow to the first side branch and to increase flow to one or more arteries distal to the first side branch vessel supplying an organ of the patient.

[0006] In another example ("Example 2"), further to the method of Example 1, the organ is one of a kidney, a brain, a pancreas, or a liver.

[0007] In another example ("Example 3"), in addition to the method of Example 1, the method includes positioning an implantable medical device to restrict blood flow in the first side branch vessel, which includes reducing flow into the first side branch and increasing flow into one or both renal arteries of the patient to improve perfusion of the kidney.

[0008] In another example ("Example 4"), in addition to the method of Example 3, the method includes positioning an implantable medical device to restrict blood flow in the first side branch vessel, including covering the first side branch vessel located proximal to a renal artery ostium.

[0009] In another example ("Example 5"), in addition to the method of any one of Examples 1-4, the method includes positioning an implantable device, which includes positioning a perfusable portion of the implantable medical device adjacent to the first side branch vessel.

[0010] In another example ("Example 6"), in addition to the method of Example 5, the method includes placing a perfusable portion adjacent to a first side branch vessel that reduces flow to the first side branch vessel by about 20% to about 30%.

[0011] In another example ("Example 7"), further to the method of any one of Examples 5-6, the perfusable portion of the implantable medical device is one or both of a stent element and a graft component.

[0012] In another example ("Example 8"), in addition to the method of Example 7, the method includes positioning a perfusable portion of a graft component adjacent to the first side branch vessel.

[0013] In another example ("Example 9"), in addition to the method of Example 7, the method includes positioning a perfusable portion, which includes positioning a perfusable portion of a stent component adjacent to the first side branch vessel.

[0014] In another example ("Example 10"), in addition to the method of any one of Examples 1-9, the method includes positioning an implantable medical device to restrict blood flow in a first side branch vessel, the first side branch being positioned proximal to one or more arteries supplying an organ of the patient.

[0015] In one example ("Example 11"), an implantable medical device for altering blood flow within a patient's blood vessel comprises a stent element and a graft component attached to at least a portion of the stent element, the graft component having a porosity configured to increase flow or pressure in the patient's renal artery by reducing flow to a first side branch disposed adjacent the graft component by about 10% to about 30% to improve renal perfusion and diuresis.

[0016] In another example ("Example 12"), in addition to the device of Example 11, the graft component includes a porous film configured to allow blood flow through the film with minimal pressure drop such that flow is reduced by about 10% to 30% within the blood vessel.

[0017] In another example ("Example 13"), in addition to the device of Example 11, the graft component includes holes configured to allow blood flow through the film.

[0018] In another example ("Example 14"), in addition to the device of Example 11, the holes are laser drilled holes in the graft component.

[0019] In one example ("Example 15"), an implantable medical device for altering blood flow within a patient's blood vessel includes a stent element configured to impose a restriction within the stent element to alter the blood flow within the vessel, the stent element responsive to pulsatile flow to increase blood flow to one or more branch vessels extending from the vessel and alter the restriction, and an anchor portion configured to engage a vascular wall of the vessel and position the stent element within the vessel.

[0020] In another example ("Example 16"), in addition to the device of Example 15, the anchor portion includes a membrane component disposed around a portion of the stent element.

[0021] In another example ("Example 17"), in addition to the device of any one of Examples 15-16, the device also includes a restricting portion including a restricting membrane component disposed around a portion of the stent element, the restricting membrane component configured to restrict the portion of the stent element, tapering the stent element, and reducing the diameter of the stent element from the proximal end to the distal end.

[0022] In another example ("Example 18"), in addition to the device of Example 17, the restriction membrane component is disposed at a distal end of the stent element and the anchor portion is at a proximal end of the stent element.

[0023] In another example ("Example 19"), in addition to any one of the devices of Examples 15-18, the stent element is configured to expand in response to pressure from pulsating flow and contract in response to a lack of that pressure, thereby maintaining pressure throughout the cardiac cycle and increasing blood flow to the side branch.

[0024] In another example ("Example 20"), in addition to the device of any one of Examples 15-19, the blood vessel is the aorta, and the stent element is configured to increase flow to the patient's renal arteries to improve renal perfusion and diuresis.

[0025] In another example ("Example 21"), in addition to the device of any one of Examples 15-19, the anchor portion is configured to face the aortic vessel wall and create a narrowed flow lumen of about 40% to about 80% in a conduit placed in the aorta distal to one or both renal arteries, thereby altering blood flow to at least one branch vessel of the aorta.

[0026] In another example ("Example 22"), in addition to the device of any one of Examples 15-19, the anchor portion is configured to face the vascular wall of the vena cava and create a narrowed flow lumen of about 40% to about 90% in a conduit placed in the vena cava distal to one or both renal veins, thereby altering blood flow through one or both renal veins.

[0027] In another example ("Example 23"), in addition to the device of Example 22, the stent element is configured to reduce blood pressure from one or both renal veins and promote blood flow through the kidney.

[0028] In another example ("Example 24"), in addition to the device of any one of Examples 15-23, the stent element is configured to increase positive pressure to one or more branch vessels throughout the cardiac cycle.

[0029] In another example ("Example 25"), in addition to the device of any one of Examples 15-24, the stent element and anchor portion are snareables configured to be retrieved.

[0030] The foregoing examples are exemplary only and should not be read to limit or otherwise narrow the scope of any of the inventive concepts otherwise provided by this disclosure. While multiple examples have been disclosed, still other embodiments will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative examples. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive in nature. [Brief description of the drawings]

[0031] The accompanying drawings are included to provide a further understanding of the disclosure, and are incorporated in and constitute a part of this specification, illustrate embodiments and, together with the description, serve to explain the principles of the disclosure.

[0032] [Figure 1] FIG. 1 illustrates an exemplary implantable medical device according to various embodiments of the present disclosure.

[0033] [Diagram 2] FIG. 2 illustrates an exemplary implantable medical device according to various embodiments of the present disclosure.

[0034] [Diagram 3] FIG. 3 illustrates an exemplary implantable medical device implanted in a patient's blood vessel, according to various aspects of the present disclosure.

[0035] [Figure 4] FIG. 4 shows an expanded view of a portion of an exemplary implantable medical device according to various embodiments of the present disclosure.

[0036] [Diagram 5] FIG. 5 illustrates an exemplary implantable medical device with varying constraints, according to various embodiments of the present disclosure.

[0037] [Figure 6] FIG. 6 illustrates an exemplary implantable medical device modified in response to pulsatile flow, according to various embodiments of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] Definitions and Terminology This disclosure is not intended to be read in a limiting manner, for example, the terms used in this application should be read broadly in the context of the meaning that the art terms ascribe to such terms.

[0039] With respect to the term imprecision, the terms "about" and "approximately" are used interchangeably and can refer to measurements including those stated and measurements reasonably close to the stated measurements. Measurements reasonably close to the stated measurements deviate from the stated measurements by a reasonably small amount, as understood and readily ascertained by those skilled in the relevant art. Such deviations can be due to measurement errors, differences in calibration of measuring and / or manufacturing equipment, human errors in reading and / or setting measurements, minor adjustments made to optimize performance and / or construction parameters considering differences in measurements relative to other components, specific implementation scenarios, such as imprecise adjustment and / or manipulation of objects by humans or machines, etc. In cases where it is determined that such reasonably small difference values ​​cannot be readily ascertained by those skilled in the relevant art, the terms "about" and "approximately" can be understood to mean ±10% of the stated value.

[0040] Description of Various Embodiments

[0041] Those skilled in the art will readily appreciate that the various aspects of the disclosure may be implemented by any number of methods and apparatus configured to perform the intended functions. It should also be noted that the accompanying drawings referred to herein are not necessarily drawn to scale and may be exaggerated to illustrate various aspects of the disclosure, and in that regard, the drawings should not be construed as limiting.

[0042] Various aspects of the present disclosure are directed to treating heart failure and / or other cardiovascular diseases, such as hypertension and hypotension, in a patient. In certain instances, the patient's condition may be exacerbated by the accumulation of excess fluid in the body (e.g., hypervolemia). Fluid accumulation can increase fluid accumulation, primarily in tissues, and increase fluid and pressure in various circulations and organs. The increased fluid and pressure, by itself or in combination with an already failing heart, can further harm the patient. As discussed in more detail below, various aspects of the present disclosure are directed to reducing the accumulation of excess fluid through the use of implantable medical devices.

[0043] Various aspects of the present disclosure are directed to implantable medical devices configured to manipulate renal blood flow hemodynamics to induce a physiologically mediated therapeutic response. The implantable medical devices discussed herein are intended, in certain instances, to increase blood flow to the kidney, thereby increasing natural diuresis and reducing excess fluid accumulation. Through this action, the device is configured to redirect blood flow to the kidney to reperfuse it, improve diuresis (increase fluid removal), and minimize / eliminate the effects of fluid overload on the heart. Renal health can include the amount of damage the kidney has sustained or continues to sustain, or a decline in function compared to the patient's baseline renal function when healthy. In certain instances, kidney damage can be quantified by measuring neutrophil gelatinase-associated lipocalin (NGAL).

[0044] The implantable medical device, in certain instances, allows for continuous and controlled fluid removal. As will be described in more detail below, the patient's vasculature near the renal arteries is complex. More specifically, the patient's vasculature may include side branches from the aorta in addition to the renal arteries. The implantable medical device may include portions of the device that are porous or perfusable to blood flow. In certain instances, the entire device is porous or perfusable to blood flow. Furthermore, certain portions of the implantable medical device may have different porosity or perfusion than other portions of the implantable medical device. In each of these instances, the implantable medical device is configured to be implanted into the main blood vessel and to alter blood flow from the main vessel to the side branch.

[0045] In certain instances, the implantable medical devices discussed herein can be implanted into other blood vessels. The implantable medical devices can promote a reduction in blood pressure or an increase in peripheral resistance to treat resistance within the vasculature. As discussed further below, this can include implantation procedures of implantable medical devices for the treatment of arteriovenous (AV) fistulas.

[0046] FIG. 1 illustrates an exemplary implantable medical device 100 according to various aspects of the disclosure. The implantable medical device 100 is shown disposed within a patient's vascular system. The patient's vascular system illustrated in FIG. 1 includes the patient's heart 102, aortic root 104, superior vena cava 106, aortic arch 108, pulmonary trunk 110, descending aorta 112, celiac artery 114, superior mesenteric artery 116, renal arteries 118, 120, inferior mesenteric artery 122, abdominal aorta 124, and iliac arteries 126, 128. The implantable medical device 100 can be disposed within the aorta proximal to the renal arteries 118, 120 as shown. Additionally, the implantable medical device 100 can be configured to increase blood flow to at least one of the renal arteries 118, 120 while maintaining substantially unrestricted blood flow within the aorta proximal to the renal arteries 118, 120. As shown, the implantable medical device 100 covers the superior mesenteric artery 116 to increase blood flow to the renal arteries 118, 120 while allowing less flow to the superior mesenteric artery 116. In certain instances, the implantable medical device 100 can be positioned to restrict flow to arteries proximal to the artery targeted for increased blood flow.

[0047] In a particular example, the implantable medical device 100 can be for enhancing perfusion of branch vessels (e.g., renal arteries 118, 120 or iliac arteries 126, 128) that originate from the aorta. The implantable medical device 100 can be conditioned by increasing resistance to blood flow through the implantable medical device 100, increasing pressure within the aorta and increasing blood flow to the branch vessels. Additionally, the implantable medical device 100 can be configured to remain within the aorta to continually increase perfusion.

[0048] The implantable medical device 100 configured to increase blood flow to at least one of the renal arteries 118, 120 can reduce fluid accumulation by increasing the amount of blood filtered by the kidney. In patients suffering from heart failure, fluid overload can be caused (at least in part) by insufficient blood flow through the kidney due to reduced cardiac output and venous congestion. The use of the implantable medical device 100 to increase blood flow to at least one of the renal arteries 118, 120 can increase renal perfusion hemodynamically, not pharmacologically. Increasing renal perfusion enhances renal filtration, thus removing fluid volume. Additionally, the implantable medical device 100 can be used to enhance the performance of a pharmacological therapy administered in combination therewith. For example, a pharmacological therapy (e.g., a diuretic and / or hypertensive drug) can be enhanced by further enhancing the patient's renal function.

[0049] In certain instances, an implantable medical device 100 configured to increase blood flow to at least one of the renal arteries 118, 120 while maintaining substantially unrestricted blood flow in the aorta proximal to the renal arteries 118, 120 can focus blood flow to one or both of the renal arteries 118, 120. Restriction proximal to the renal arteries 118, 120 can direct blood flow to other areas supplied by the aorta, such as the celiac artery 114, the superior mesenteric artery 116, or the brain. Thus, in certain instances, the implantable medical device 100 can be positioned within the aorta of a patient proximal to (or overlapping) the renal arteries 118, 120. As a result, increased blood flow to one or both of the renal arteries 118, 120 can increase blood flow to at least one of the kidneys, which can increase fluid removal from the circulation and reduce fluid and pressure buildup in various circulation and organs.

[0050] The implantable medical device 100 provides a non-pharmaceutical approach to increasing urine production (diuresis) and / or modifying systemic blood pressure. Patients may experience drug resistance, inaccurate dosing, or undesirable side effects. When medications fail, aquapheresis or hemodialysis can be used to filter fluids directly from the blood, but these solutions are relatively invasive and disruptive to the patient's lifestyle and mobility. Furthermore, aquapheresis or hemodialysis may also cause hemodynamic instability with associated cardiovascular complications, kidney damage, infection, and / or require capital equipment.

[0051] The implantable medical device 100 can change peripheral resistance when implanted percutaneously or surgically, temporarily or permanently, and can be adjustable to meet the needs of the patient. The implantable medical device 100 can remain in the body after the implantation procedure for as long as the patient requires the intervention. The implantable medical device 100 can be implanted for hours, days, or even years.

[0052] The paired branch vessels separated from the aorta can be angled or not perpendicular to the aorta. Additionally, the branch vessels arising from the unpaired aorta do not always branch at the same angle (e.g., the vessels extending from the aorta are specific to the patient's anatomy). As discussed in more detail below, the implantable medical devices discussed herein can be positioned to at least partially overlap the arteries proximal to the renal arteries 118, 120. The implantable medical devices discussed herein allow lateral blood flow into the overlapping arteries such that the implantable medical device reduces blood flow into the arteries. As a result, increased blood flow into one or both of the renal arteries can increase blood flow to at least one kidney, which increases fluid removal from the circulation and reduces fluid and pressure buildup in various circulations and organs. The implantable medical device allows for lateral blood perfusion over the length of the device to address implantability difficulties due to branch vessel geometry within a particular patient's anatomy.

[0053] The exemplary implantable medical device 100 illustrated in Figure 1 is not intended to suggest limitations on the scope of use or functionality of the embodiments of the present disclosure disclosed throughout this specification. The exemplary implantable medical device 100 should not be interpreted as having dependencies or requirements relating to any single component or combination of components illustrated herein. Furthermore, any one or more of the components illustrated in Figure 1 may, in embodiments, be integrated with various of the other components illustrated therein (and / or components not illustrated).

[0054] 2 illustrates an exemplary implantable medical device 200 according to various aspects of the present disclosure. The implantable medical device 200 is configured to alter blood flow within a patient's blood vessel, as described in detail above. The implantable medical device 200 includes a stent element 202 and a graft component 204 attached to at least a portion of the stent element 202.

[0055] In certain instances, the graft component 204 is at least partially perfusable to allow flow to a side branch while maintaining flow through the vessel. The graft component 204 can include pores, as described in further detail below with reference to FIG. 4, that are configured to allow blood flow through the graft component 204. In certain instances, the graft component 204 includes a porous film configured to allow blood flow through the film with minimal pressure drop within the vessel.

[0056] As described above and in further detail below with reference to Figure 3, the implantable medical device 200 may be implanted within a patient's aorta and configured to restrict or increase flow to at least one of the celiac artery, hepatic artery, and mesenteric artery. In certain examples, the implantable medical device 200 may increase or decrease flow to branch vessels (or vessel pairs), which may include the gastric artery, splenic artery, accessory renal artery (pair), phrenic artery (pair), gonadal artery (pair), lumbar artery (pair), and sacral artery (unpaired).

[0057] When implanted in the aorta, the device 200 is configured to redirect blood flow to at least one of the renal arteries by diverting fluid within the aorta. To achieve increased renal perfusion, resistance to blood flow distal to the renal arteries can be increased, thereby decreasing distal perfusion. Increased renal perfusion promotes renal production and thus removal of fluid volume. In certain instances, the device 200 is configured to create a narrowed flow lumen of about 40% to about 80% within the patient's aortic conduit at least partially distal to the renal arteries, altering blood flow to at least one branch vessel of the aorta (e.g., one or both of the renal arteries). In certain instances, the induced restriction is about 50% to about 70% of the nominal flow rate.

[0058] When implanted in the vena cava, device 200 can enhance perfusion from tributary vessels (e.g., renal veins) terminating in the vena cava by altering the pressure within the vena cava to alter blood flow from the tributary vessels of the vena cava. In certain instances, device 200 can be configured to create a narrowed flow lumen of about 40% to about 90% within a conduit located in the vena cava distal to at least one tributary vessel. Use of a flow restriction device, discussed in more detail below, by lowering pressure within the renal vein can increase renal perfusion hemodynamically, rather than pharmacologically.

[0059] In certain examples, device 200 is placed in a blood vessel other than the aorta or venous sinus. In these examples, device 200 may be configured to alter blood flow through a lumen to restrict blood flow in the vessel and induce a physiologically mediated therapeutic response in the patient. In certain examples, device 200 is configured to induce a physiologically mediated therapeutic response to include increasing peripheral resistance in the vessel. Device 200 may be configured to treat a fistula in the vessel and increase peripheral resistance in the vessel, as described in more detail below.

[0060] FIG. 3 illustrates an exemplary implantable medical device 200 implanted in a blood vessel 300 of a patient, according to various aspects of the disclosure. In certain instances, the implantable medical device 200 can be used in a method to alter blood flow 314 within a blood vessel of a patient. As illustrated in FIG. 3, the implantable medical device 200 is implanted within the aorta. The implantable medical device 200, including a stent element 202 and a graft component 204 attached to at least a portion of the stent element 202, can be delivered to a target location within the blood vessel (e.g., the aorta). The implantable medical device 200 is positioned to at least partially direct flow into one or more side branches 308, 310, 312 from the blood vessel (aorta) 300.

[0061] In altering blood flow within the blood vessel 300, the implantable medical device 200 is configured to be delivered within the blood vessel and restrict blood flow to one or more first branch blood vessels 308, 310 to reduce flow to one or both of the first branches 308, 310 and increase flow to one or more arteries (such as blood vessel 312) that supply an organ of the patient. In certain examples, the organ is one of the patient's adrenal glands, testes or ovaries, pancreas, intestine, appendix, liver, stomach, gallbladder, duodenum, spleen, spine, bladder, or muscle. As described in more detail below, the implantable medical device 200 is positioned to restrict blood flow to one or more first side branch blood vessels 308, 310 that are proximal to one or more arteries 312 that supply an organ of the patient.

[0062] In an example where the organ is a kidney, the branch intended for greater flow is one or more renal arteries. By positioning the implantable medical device 200 in this manner, the graft component 204 and / or stent component 202 restrict blood flow in one or more branches 308, 310 to increase flow to one or more arteries (such as blood vessel 312). In a particular example, blood vessel 312 can be a renal artery with increased inflow to one or both renal arteries of a patient, thereby improving renal perfusion. In a particular example, the graft component 204 and / or stent component 202 are configured to restrict blood flow to one or more first side branch vessels 308, 310 located proximal to a renal artery ostium by covering said one or more first side branch vessels 308, 310.

[0063] To reduce blood flow to one or more side branch vessels 308, 310, the perfusable portion of the implantable medical device 200 is positioned adjacent to one or more first side branch vessels 308, 310. In certain instances, the entire implantable medical device 200 is perfusable, allowing lateral blood flow. Blood flow does not flow laterally from the implantable device 200 partially because the implantable medical device 200 is in contact with the vessel wall 300. The perfusable portion, i.e., the portion positioned adjacent to the one or more first side branch vessels 308, 310, reduces flow to the one or more first side branch vessels 308, 310 by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, or any value therebetween. In certain instances, the graft component 204 is perfusable, thus controlling the amount of blood flow to the one or more branch vessels 308, 310. The porosity of the graft component 204 may be tailored to achieve a desired amount of flow reduction into one or more blood vessels 308, 310. In other examples, the stent component 202 is perfusable and controls the amount of flow into one or more blood vessels 308, 310. The stent component 202 may be woven or positioned to achieve a desired amount of flow reduction into one or more blood vessels 308, 310. Additionally, in other examples, the combination of the graft component 204 and the stent component 202 may control the amount of flow into one or more blood vessels 308, 310. In certain examples, the porosity of the graft component 204 and the weave or positioning of the stent component 202 are tailored to achieve a desired amount of flow reduction into one or more blood vessels 308, 310. The stent component 202 may be a wound wire structure or laser cut from a tube.

[0064] In certain instances, the graft component 204 of the implantable medical device 200 includes one or more porous or perfusable portions. The implantable medical device 200 may be positioned such that the porous or perfusable portions of the graft component 204 of the implantable medical device 200 are positioned adjacent to one or more side branches 308, 310, 312 to direct flow to the one or more side branches 308, 310, 312 distal to the branch vessel 308, 310, 312 in which the implantable medical device 200 is positioned. The implantable medical device 200 may alter pressure within the aorta to increase or decrease blood flow 314 to the side branches 308, 310, 312 (such as the renal arteries). Increasing pressure at or distal to a target branch, such as the renal arteries 118, 120 or the iliac arteries 126, 128, by the implantable medical device 200 (shown at the top of FIG. 1) can increase blood flow 314 to the distal region (e.g., the renal arteries 118, 120 and / or the iliac arteries 126, 128, depending on the placement of the implantable medical device 200).

[0065] In certain instances, the implantable medical device 200 can produce long-term or chronic physiological changes in a patient. The implantable medical device 200 can generate a neurohormonal response that alters flow to the kidney and changes the patient toward normal kidney function. The kidney is a feedback regulator of systemic pressure through the patient's body. The implantable medical device 200 provides a non-pharmaceutical means of altering flow to the kidney and affecting the kidney's natural feedback mechanism for regulating systemic pressure.

[0066] Adjusting the degree of hemodynamic change in renal perfusion can provide patient-specific adjustments to regulate blood pressure. Adjusting the aortic fluid flow rate provided by the implantable medical device 200 can affect the renal artery pressure and / or flow rate, which can then be manifested as temporary or long-term changes in systemic blood pressure. The changes in renal-mediated blood pressure levels induced by the implantable medical device 200 can provide therapeutic benefits in themselves. Similarly, the changes induced in renal-mediated blood pressure levels by the implantable medical device 200 can be used in combination with various blood pressure medications to optimize individualized blood pressure management.

[0067] The implantable medical device 200 can occlude proximal branches of side branches 308, 310 (e.g., renal arteries) by about 5% to about 30% to increase blood flow 314 to the kidney. The porosity of the implantable medical device 200 can be adjusted to achieve an increase in blood flow 314 to the kidney by about 5% to about 30%. As described in more detail below with reference to FIG. 4, the size, location, number and perfusion of the pores can be varied to achieve a desired blood flow.

[0068] 4 illustrates an enlarged view of a portion of an exemplary implantable medical device 200 according to various aspects of the present disclosure. As shown in FIG. 4, the graft component 204 coupled to the stent component 202 can include pores 414 configured to allow blood flow through the film. The pores 414 can be perforations or laser drilled holes in the graft component 204. The openings or pores 414 in the graft component 204 can further provide perfusion to side branch vessels. For example, the graft component 204 can have perfusion regions that include the pores 414 and exclusion regions that are substantially free of the pores 414.

[0069] As shown in FIG. 4, the graft component 204 can include additional pores 416 having a different porosity than the pores 414. The additional pores 416 and the pores 414 can be of different sizes, shapes and / or locations. As a result, in certain examples, the graft component 404 includes a first portion having a porosity configured to direct flow to one or more side branches from a blood vessel by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, or any value therebetween, to improve renal perfusion and diuresis, and a second component that is non-porous and configured to inhibit blood flow radially through the second component. Additionally, the graft component 204 can include multiple layers having different porosities.

[0070] 5 illustrates an exemplary implantable medical device 500 having varying restriction in accordance with various aspects of the present disclosure. The implantable medical device 500 includes a stent element 506 and an anchor portion 502. The implantable medical device 500 is shown positioned within a blood vessel 300 of a patient.

[0071] The stent element 506 is configured to impose a restriction to alter blood flow within the vessel and increase blood flow to one or more branch vessels 308, 310 extending from the vessel 300, and to change the restriction in response to pulsatile flow, as shown in FIG. 6 and discussed in more detail with reference thereto. The stent element 506 is configured to expand in response to pressure from the pulsatile flow and to contract in response to a lack of said pressure. Furthermore, the vessel 300 is an aorta, and the stent element 506 is configured to increase flow to the patient's renal arteries to improve renal perfusion and diuresis. In a particular example, the stent element 506 is configured to expand in response to pressure from the pulsatile flow and to contract in response to a lack of said pressure to ensure pressure and increased blood flow to the side branches throughout the cardiac cycle.

[0072] The anchor portion 502 of the implantable medical device 500 is configured to engage the vessel wall of the blood vessel 300 and position the stent element 500 within the blood vessel 300. The anchor portion 502 may include a membrane or graft component 508 that reduces the chance of thrombosis. The membrane or graft component 508 of the anchor portion 520 may contact the vessel wall.

[0073] In a particular example, the implantable medical device 500 includes a restricting portion 504 that includes a limiting membrane component 510 disposed about a portion of a stent element 506. The limiting membrane component 510 is configured to restrict a portion of the stent element 506 and tapering the stent element and decreasing the diameter of the stent element 506 from the proximal end to the distal end. As shown, the limiting membrane component 510 is disposed at the distal end of the stent element 506 and the anchor portion 502 is at the proximal end of the stent element 506.

[0074] In certain instances, and as shown, the stent element 506 can partially occlude a side branch (e.g., proximal to the renal artery) 308, 310 by about 5% to about 30% to increase blood flow to the kidney. The implantable medical device 500 can be implanted to have lateral perfusion and restrict blood flow to one or more arteries 308, 310 proximal to the renal artery (or other artery supplying an organ) to increase blood flow to a renal artery (or other artery supplying an organ) distal to the location of the implantable medical device 500. In these instances, the stent element 506 is perfusable as discussed in detail above.

[0075] In certain instances, the anchor portion 502 is placed upstream of the renal artery where the landing zone, i.e., the portion of the stent element 506 between the anchor portion 502 and the restricting membrane component 510, is occluded. In other instances, the anchor portion 502 may be placed below the kidney with the same clinical effect. The implantable medical device 500 is configured to perform in many locations that are typically afflicted by disease or acute arterial angulation. Additionally, the restricting membrane component 510 facilitates the expansion and contraction of the stent element 506.

[0076] In certain instances, when the increased flow encounters the implantable medical device 500, there is more flow to the upstream vessel due to flow obstruction by the implantable medical device 500. As the implantable medical device 500 stretches, flow to the kidney (or other branch vessel) increases due to the restrictive membrane component 510 restricting flow. When the implantable medical device 500 contracts and snaps back upstream, the implantable medical device 500 also pushes blood into the kidney (or other side branch) due to the implantable medical device 500 drawing back a small amount of blood upstream with the implantable medical device 500. As a result, the implantable medical device 500 increases the positive pressure to the kidney (or side branch) throughout the cardiac cycle. In certain instances, the implantable medical device 500 is snareable or retrievable by the clinician during the procedure or at a later date.

[0077] In other examples, the stent element 506 is not perfusable and the implantable medical device 500 is not deployed as shown. In these examples, the stent element 506 can increase or decrease the fluid flow rate in the vessel (aorta) 300 distal to the side branches (e.g., renal arteries) 308, 310 by about 5% to about 30% compared to normal flow. In certain examples, the stent element 506 is configured to induce a stenosis of the patient's aorta at least partially distal to the side branches (e.g., renal arteries) 308, 310 by about 40% to about 80%, altering blood flow to one or more side branches (e.g., renal arteries) 308, 310 while maintaining substantially unrestricted blood flow in the vessel (aorta) 300 proximal to the one or more side branches (e.g., renal arteries) 308, 310. In certain examples, the induced stenosis is about 50% to about 70%. Clinically, measurements of ankle pressure, Doppler ultrasound velocity, ankle-brachial pressure index or other hemodynamic parameters of the lower extremities can be used to optimize the size of the induced constriction while ensuring adequate limb perfusion.

[0078] When implanted in the aorta, the device 500 is configured to redirect blood flow to at least one of the renal arteries by diverting fluid within the aorta. To achieve increased renal perfusion, resistance to blood flow distal to the renal arteries can be increased, thereby decreasing distal perfusion. Increased renal perfusion promotes renal production and thus removal of fluid volume. In certain instances, the device 500 is configured to create a narrowed flow lumen of about 40% to about 80% within the patient's aortic conduit at least partially distal to the renal arteries, altering blood flow to at least one branch vessel of the aorta (e.g., one or both of the renal arteries). In certain instances, the induced restriction is about 50% to about 70% of the nominal flow rate.

[0079] When implanted in the vena cava, the device 500 may enhance perfusion from tributary vessels (e.g., renal veins) terminating in the vena cava by altering the pressure within the vena cava to alter blood flow from the tributary vessels of the vena cava. In certain instances, the device 500 may be configured to create a narrowed flow lumen of about 40% to about 90% within a conduit located in the vena cava distal to at least one tributary vessel. Use of a flow restriction device, discussed in more detail below, by lowering pressure within the renal vein may increase renal perfusion hemodynamically, rather than pharmacologically.

[0080] FIG 6 illustrates an exemplary implantable medical device 500 that is altered in response to pulsatile flow, according to various aspects of the disclosure. Pulsatile flow, represented by an R wave of an EKG, is shown adjacent the implantable medical device 500 contracting and expanding. The stent elements 506 of the implantable medical device 500 are configured to expand in response to pressure from the pulsatile flow and to contract in response to a lack of said pressure, as shown in FIG 6. The stent elements 506 impose an additional restriction in the expanded configuration, restricting blood flow to proximal side branch vessels of the artery where increased blood flow is desired.

[0081] In certain instances, patients with heart failure (such as late-stage heart failure) may experience an increased state of the sympathetic nervous system due in part to a decrease in cardiac output (blood pressure and flow of one or both kidneys). One compensation for this state is to generate signals to maintain cardiac output, which places additional strain on the heart (myocardial oxygen demand). The implantable medical devices and methods including implantable medical devices discussed herein are directed to increasing renal pressure (mean or peak systolic) to reduce stimulation of neurohormonal responses (e.g., reducing sympathetic activation of the nervous system). As a result of the reduction in activation of the sympathetic nervous system by the implantable medical device or methods including the implantable medical device, resting heart rate and blood pressure can be reduced.

[0082] Furthermore, in certain instances, patients with heart failure (such as late-stage heart failure) may have activation of the renin-angiotensin-aldosterone system (RAAS), which causes impaired blood flow to the kidneys, in part due to reduced cardiac output. The result of elevated RAAS is to generate signals that stimulate adverse myocardial structural changes. The implantable medical devices and methods including implantable medical devices discussed herein are directed to increasing intrarenal pressure (mean or peak systolic) to reduce stimulation of the RAAS. As a result of reduced activation of the RAAS by the implantable medical device or methods including implantable medical devices, activation of the sympathetic nervous system can be reduced and adverse cardiac remodeling can be attenuated.

[0083] Previous studies of implantable medical devices implanted in the aorta have been used to evaluate the response of dogs with induced heart failure (coronary microembolization resulting in an ejection fraction of about 30%). The hemodynamic status observed in the test group compared to the control group showed improved cardiac function and reduced sympathetic tone. For example, heart rate and mean arterial pressure were reduced, but contractility was increased compared to the control group. These comparative results were supported by positive shifts in biomarkers such as proBNP and NGAL compared to the control group. As an example, animals with the implant had a creatinine content about 21% higher, urine production increased by about 35%, and the increase in serum creatinine as a result of diuretic administration was reduced by about 52%. These results indicate that implantable medical devices, such as implantable medical devices that direct blood to the kidneys or restrict blood flow in the aorta distal to the renal arteries, may help to alleviate symptoms of fluid overload and cardiac overload associated with heart failure. The device has been shown to increase blood pressure proximal to the stenosis, thereby increasing renal perfusion pressure and therefore renal perfusion. A secondary effect of the device is a reduction in activation of the RAAS system. The efficacy of the device was based on assessment of central hemodynamics, left ventricular (LV) function and renal function.

[0084] Furthermore, previous studies have found that induced stenosis has little effect on flow or pressure until it reaches about 40%, after which the impact depends on the arterial diameter and blood flow velocity. However, based on the animal studies mentioned above, it has been discovered that there is a threshold above which the impact increases dramatically. The regime of stenosis based on these results is about 40% to about 80%, more specifically about 50% to about 70%. Clinically, measurements of ankle pressure, Doppler ultrasound velocity or other hemodynamic parameters of the lower limb can be used to optimize the magnitude of induced stenosis while ensuring adequate limb perfusion.

[0085] Additionally, while in certain instances the above devices describe a diametric restriction of the aorta or vena cava, the length of the restriction portion can also affect the amount of restriction of the aorta or vena cava, and thus the length of the restriction portion and the diameter or circumference of the restriction portion can be varied to achieve a desired percentage stenosis or restriction.

[0086] Furthermore, the device discussed herein can be implanted into blood vessels for the treatment of arteriovenous (AV) fistula. The formation of AV fistula can lead to a decrease in peripheral resistance in the vascular system. Implanting the device discussed herein at or adjacent to the AV fistula can increase flow resistance to a nominal level and counteract the decrease in peripheral resistance caused by the AV fistula. In certain instances, the device is implanted distal to the AV fistula, proximal to the AV fistula, or across the AV fistula.

[0087] Examples of synthetic polymers that may be used as graft components include, but are not limited to, nylon, polyacrylamide, polycarbonate, polyformaldehyde, polymethylmethacrylate, polytetrafluoroethylene, polytrifluorochloroethylene, polyvinyl chloride, polyurethane, elastomeric organosilicon polymers, polyethylene, polypropylene, polyurethane, polyglycolic acid, polyester, polyamide, mixtures, blends and copolymers thereof that are suitable as graft materials. In one embodiment, the graft is made from the classes of polyesters such as polyethylene terephthalates, including DACRON® and MYLAR®, and polyaramids such as KEVLAR®, polyfluorocarbons such as polytetrafluoroethylene (PTFE) with or without copolymerized hexafluoropropylene (TEFLON® or GORE-TEX®), and porous or non-porous polyurethanes. In a particular example, the graft comprises an expanded fluorocarbon polymer (particularly PTFE) material as described in British Patent No. 1,355,373, British Patent No. 1,506,432 or British Patent No. 1,506,432 or US Patent No. 3,953,566, US Patent No. 4,187,390 or US Patent No. 5,276,276, which are incorporated by reference in their entirety. Preferred classes of fluoropolymers include polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), copolymers of tetrafluoroethylene (TFE) and perfluoro(propyl vinyl ether) (PFA), homopolymers of polychlorotrifluoroethylene (PCTFE) and its copolymers with TFE, ethylene-chlorotrifluoroethylene (ECTFE), copolymers of ethylene-tetrafluoroethylene (ETFE), polyvinylidene fluoride (PVDF) and polyvinylidene fluoride (PVF). Particularly preferred is ePTFE due to its widespread use in vascular prostheses. In certain instances, the graft comprises a combination of the materials listed above. In certain instances, the graft is substantially impermeable to bodily fluids.The substantially impermeable graft can be made from materials that are substantially impermeable to bodily fluids, or can be constructed from permeable materials that have been treated or manufactured to be substantially impermeable to bodily fluids (e.g., by layering different types of materials as described above or known in the art).

[0088] Additional examples of graft materials include, but are not limited to, vinylidine fluoride / hexafluoropropylene (HFP), tetrafluoroethylene (TFE), vinylidene fluoride, 1-hydropentafluoropropylene, perfluoro(methyl vinyl ether), chlorotrifluoroethylene (CTFE), pentafluoropropene, trifluoroethylene, hexafluoroacetone, hexafluoroisobutylene, fluorinated poly(ethylene-co-propylene) (FPEP), poly(hexafluoropropene) (PHFP), poly(chlorotrifluoroethylene) (PCTFE), poly(vinylidene fluoride), (PVDF), poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TFE), poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-HFP), poly(tetrafluoroethylene-co-hexafluoropropene) (PTFE-HFP), poly(tetrafluoroethylene-co-vinyl alcohol) (PTFE-VAL), poly(tetrafluoroethylene-co-vinyl acetate) (PTFE-VAC), poly(tetrafluoroethylene-co-propene) (PTFEP), poly(hexafluoropropene-co-vinyl alcohol) (PHFP-VAL), poly(ethylene-co-tetrafluoroethylene) ( Poly(ethylene-co-hexafluoropropene) (PEHFP), poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) and combinations thereof, as well as additional polymers and copolymers described in U.S. Patent Publication No. 2004 / 0063805, which are incorporated herein by reference in their entirety for all purposes. Additional polyfluoro copolymers include tetrafluoroethylene (TFE) / perfluoroalkyl vinyl ether (PAVE). PAVE can be perfluoromethyl vinyl ether (PMVE), perfluoroethyl vinyl ether (PEVE) or perfluoropropyl vinyl ether (PPVE), essentially as described in U.S. Patent Publication No. 2006 / 0198866 and U.S. Patent No. 7,049,380, both of which are incorporated herein by reference in their entirety for all purposes.Other polymers and copolymers include polylactides, polycaprolactone-glycolides, polyorthoesters, polyanhydrides, polyamino acids, polysaccharides, polyphosphazenes, poly(ether-ester) copolymers such as PEO-PLLA or blends thereof, polydimethyl-siloxanes, poly(ethylene-vinyl acetate), acrylate-based polymers or copolymers such as poly(hydroxyethylmethylmethacrylate, polyvinylpyrrolidinone, fluorinated polymers such as polytetrafluoroethylene, cellulose esters and any of the polymers and copolymers described in U.S. Publication No. 2004 / 0063805, which is incorporated herein by reference in its entirety.

[0089] As discussed herein, the graft component can be attached to the self-expanding stent component by using a connecting member that is a generally flat ribbon or tape having at least one generally flat surface. In a particular example, the tape member is made of expanded PTFE (ePTFE) coated with an adhesive. The adhesive can be a thermoplastic adhesive. In a particular example, the thermoplastic adhesive can be fluorinated ethylene propylene (FEP). More specifically, the FEP coated side of the ePTFE can be contacted toward the outer surface of the self-expanding stent and graft component, thus attaching the self-expanding stent to the graft component. Materials and methods for attaching the stent to the graft are described in U.S. Patent No. 6,042,602 to Martin, which is incorporated herein by reference for all purposes.

[0090] The stent elements discussed herein can be manufactured from a variety of biocompatible materials. These materials can include 316L stainless steel, cobalt-chromium-nickel-molybdenum-iron alloys ("cobalt-chromium"), other cobalt alloys such as L605, tantalum, nickel-titanium alloys (such as Nitinol), or other biocompatible metals. In certain instances, as discussed in detail above, the stent (and graft) can be self-expanding. The prosthesis can be balloon expandable.

[0091] A variety of materials, including superelastic alloys of various metals such as Nitinol, are suitable for use in these stents. The primary requirement of the material is that it be adequately elastic when processed into very thin sheets or small diameter wires. Various stainless steels that have been physically, chemically or otherwise treated to produce high elasticity are suitable, as are other alloys such as cobalt chromium alloys (e.g., ELGILOY®), platinum / tungsten alloys, and especially nickel-titanium alloys (e.g., Nitinol).

[0092] Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. For example, while the above embodiments refer to certain features, the scope of the present invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations that fall within the scope of the claims, together with all equivalents thereof. The aspects of the present invention are listed below. (Aspect 1) 1. An implantable medical device for altering blood flow in a blood vessel of a patient, comprising: A stent element, and a graft component attached to at least a portion of the stent element. wherein the graft component is at least partially perfusable through a porous portion to allow flow to a side branch while maintaining flow through the blood vessel, and wherein the implantable medical device is positionable proximal to a renal artery of a patient to increase flow or pressure in the renal artery of the patient by reducing flow to a side branch located adjacent to the graft component by about 10-30%. (Aspect 2) 1. An implantable medical device for altering blood flow in a blood vessel of a patient, comprising: a stent element configured to impose a restriction within the stent element to alter the blood flow within the blood vessel, the stent element increasing blood flow to one or more branch vessels extending from the blood vessel and altering the restriction in response to pulsatile flow; and an anchor portion configured to engage a vessel wall of the vessel and position the stent element within the vessel; wherein the implantable medical device is implantable proximal to a renal artery of a patient. (Aspect 3) 3. The device of embodiment 2, wherein the anchor portion comprises a membrane component disposed about a portion of the stent element. (Aspect 4) The device of embodiment 2 or embodiment 3, further comprising a restricting portion comprising a restricting membrane component disposed around a portion of the stent element, the restricting membrane component configured to restrict the portion of the stent element, tapering the stent element, and reducing a diameter of the stent element from the proximal end to the distal end. (Aspect 5) The device of embodiment 4, wherein the limiting membrane component is disposed at a distal end of the stent element and the anchor portion is at a proximal end of the stent element. (Aspect 6) The device of any one of aspects 2 to 5, wherein the stent element is configured to expand in response to pressure from pulsating flow and contract in response to a lack of such pressure, thereby ensuring pressure throughout the cardiac cycle and increasing blood flow to the side branch. (Aspect 7) The device of any one of aspects 2-6, wherein the blood vessel is an aorta and the stent element is configured to increase flow to the patient's renal arteries to improve renal perfusion and diuresis. (Aspect 8) The device of any one of aspects 2-7, wherein the anchor portion is configured to face the aortic vascular wall and create a narrowed flow lumen of about 40% to about 80% in a conduit placed in the aorta distal to one or both renal arteries, thereby altering blood flow to at least one branch vessel of the aorta. (Aspect 9) The device of any one of aspects 2-7, wherein the anchor portion is configured to face the vascular wall of the vena cava and create a narrowed flow lumen of about 40% to about 90% in a conduit placed in the vena cava distal to one or both renal veins, thereby altering blood flow through one or both renal veins. (Aspect 10) The device of embodiment 9, wherein the stent element is configured to reduce blood pressure from one or both renal veins and promote blood flow through the kidney. (Aspect 11) The device of any one of aspects 2-10, wherein the stent element is configured to increase positive pressure to one or more branch vessels throughout the cardiac cycle. (Aspect 12) The device of any one of embodiments 2-11, wherein the stent element and anchor portion are snareable configured to be retrieved. (Aspect 13) The device of embodiment 1, wherein the device is configured to vary flow to the side branch in response to pulsatile flow.

Claims

1. 1. An implantable medical device for altering blood flow in a blood vessel of a patient, comprising: A stent element, and a graft component attached to at least a portion of the stent element. the graft component is at least partially perfusable through a porous portion to allow flow to a side branch while maintaining flow through a blood vessel, and the implantable medical device is positionable proximal to a renal artery of a patient to increase flow or pressure in the renal artery of the patient by reducing flow to a side branch located adjacent to the graft component by about 10-30%, and is configured to vary flow to the side branch in response to pulsatile flow.

2. The device of claim 1, wherein the device is configured to expand in response to an increase in pressure and to contract in response to a decrease in pressure.

Images